Our goal is to develop a practical method for the treatment of diabetic humans by transplantation of the fetal pancreas. A rat model system has been developed in which a single fetal pancreas will grow to completely reverse streptozotocin-diabetes and contain 22% as much insulin as an adult pancreas. The fetal organ can be frozen for an indefinite period without loss of function. Additional studies proposed in rat model include (1) the extent of normalization of the balance of 6 enzymes regulating key steps in liver metabolism, (2) correlation of glucokinase activity in the pancreas with the glucose signal for insulin release and regulatory factors on glucokinase activity, (3) diminution of allograft rejection by selection of developmental stage of the donor organ or by organ culture. Preparations for applications of this system to human diabetics will include (1) developmental biochemistry and ultrastructure of the human fetal pancreas for selection of the optimal developmental stage (2) cryopreservation methods for permanent storage and banking (3) study of development of histocompatability antigens in the human fetus and techniques for matching fetal lymphocytes with recipient lymphocytes.